The object of this proposal is to determine the complete three-dimensional structure of every kinetically-significant step in the mechanistic pathway of yeast triose phosphate isomerase. This will be done by the technique of protein x-ray crystallography. The special nature of the isomerase reactions means that one enzyme-substrate complex can be studied diectly, without recourse to unusual techniques; the other Michaelis complex is accessible by means of low-temperature crystallography. These structures will be correlated with the detailed information already available from the isotope exchange studies of Knowles and the chemical modification studies of Hartman and Wolfenden to provide new insights into the origin of the catalytic power of triose phosphate isomerase.